The compound ingenol-3-angelate (PEP005) [Sayed, M.D. et.al.; Experienta, (1980), 36, 1206-1207] can be isolated from various Euphorbia species, and particularly from Euphorbia peplus [Hohmann, J, et. al; Planta Med., (2000), 66, 291-294] and Euphorbia drummondii by extraction followed by chromatography as described in U.S. Pat. No. 7,449,492. Ingenol has previously been used as a starting point for the semi-synthetic preparation of ingenol-3-esters [Sorg, B. et. al, Z. Naturforschung, (1982), 37B, 748-756] and ingenol-3-ester derivatives [Appendino et. al., Eur. J. Org. Chem. (1999), 3413; Opferkuch et.al., Z. Naturforschung, (1981), 36B, 878], However, the preparation of ingenol-3-angelate and ingenol-3-angelate derivatives from ingenol has not been described. PCT/DK2011/000081 describes the method of preparing ingenol-3-angelate from ingenol by reacting one or both hydroxyl groups in positions 5 and 20 of ingenol with suitable hydroxyl protecting agents followed by esterifying the hydroxyl group at the 3-position and finally removing the hydroxyl protecting groups to obtain ingenol-3-angelate. The present invention discloses a method for obtaining ingenol-3-angelate from 20-deoxy-ingenol derivatives extractable from Euphorbia plants.
